WO2004071505A2 - Acides amines de type d radiomarques, utilises pour la tomographie monophotonique d'emission et la tomographie par emission de positons ainsi que dans la therapie isotopique systemique - Google Patents

Acides amines de type d radiomarques, utilises pour la tomographie monophotonique d'emission et la tomographie par emission de positons ainsi que dans la therapie isotopique systemique Download PDF

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Publication number
WO2004071505A2
WO2004071505A2 PCT/US2004/003829 US2004003829W WO2004071505A2 WO 2004071505 A2 WO2004071505 A2 WO 2004071505A2 US 2004003829 W US2004003829 W US 2004003829W WO 2004071505 A2 WO2004071505 A2 WO 2004071505A2
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amino acid
phe
amino acids
radioactive
uptake
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PCT/US2004/003829
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WO2004071505A3 (fr
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John R. Mertens
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Mallinckrodt Inc.
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/0497—Organic compounds conjugates with a carrier being an organic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • the present invention relates to new radiolabelled D-amino acids, to pharmaceutical compositions comprising them and to their use in diagnosis, in particular with SPECT and PET, and in therapy, such as systemic radionuclide therapy.
  • Positron emission tomography is a scanning technique used in conjunction with small amounts of radiolabelled compounds.
  • a very small amount of a radiolabelled compound is inhaled by or injected into the patient.
  • the injected or inhaled compound accumulates in the tissue to be studied.
  • positrons When a positron collides with an electron (negatively charged), they are both annihilated, and two photons (light particles) are emitted.
  • the photons move in opposite directions and are picked up by the detector ring of the PET scanner.
  • a computer uses this information to generate three-dimensional, cross-sectional images that represent the biological activity where the radiolabeled compound has accumulated.
  • PET is often performed with the radioactive tracer 18 F-deoxyglucose (FDG). All living cells utilize glucose. Some cells metabolize glucose faster than others. Cancer cells are hyperactive and divide quickly, and therefore metabolize the injection of the radioactive tracer FDG faster than normal cells. On a PET scan, cancer cells appear "hot” and significantly more prominent than normal cells.
  • FDG F-deoxyglucose
  • SPECT single photon emission computed tomography
  • PET single photon emission computed tomography
  • SPECT is similar to PET, but the compounds used contain heavier, longer-lived radioactive atoms that emit high-energy photons, called gamma rays, instead of positrons.
  • SPECT is used for many of the same applications as PET, and is less expensive than PET.
  • Systemic radionuclide therapy is a form of radiotherapy that involves administering the source of the radiation into the patient.
  • systemic radionuclide therapy the physiology of the disease provides a major contribution to the therapy ultimately resulting in the delivery of the radionuclide to the tumor.
  • a radioactive material that will be delivered to the tumor by the patient's own physiologic processes, it is possible to deliver a large dose of radiation to certain tumors with a minimal amount of patient manipulation.
  • L-amino acids are already used in clinical studies, such as 3- I-alpha-methyl-L-tyrosine (L- IMT) for SPECT (Biersack et al. (1989) J. Nucl. Med. 30:110; Jager et al. (2001) Nucl. Med. Comm. 22(1):87) and 2- 18 F-L-tyrosine (Coenen et al.
  • L- 18 FET 0-(2- I8 F- ethyl-L-tyrosine
  • L- 18 FMT 18 F-alpha- methyl-L-tyrosine
  • the uptake of 2- 18 F-L-tyrosine in inflammatory lesions is lower than that of 18 F-FDG, used for routine PET diagnosis of tumours.
  • a drawback limiting the applicability of L- IMT, L- FET and L- FMT is the high renal accumulation.
  • SPECT and PET are techniques that can play an important role therein. However, new and better tracer molecules for use in these techniques will always be necessary.
  • tumour tracers for SPECT 2- 123 I-L-tyrosine (2- 123 I-L-Tyr) and 2- 123 I-L-phenylalanine (2- I23 I-L-Phe).
  • RIM rat rhabdomyosarcoma cells
  • WiDr human colonadenocarcinoma cells
  • the L transporter is a major nutrient transport system responsible for Na + - independent transport of large neutral amino acids including synthetic amino acids by an obligatory exchange mechanism coupled to an anti-port system.
  • the heterodimeric L transporter contains subunits named LAT1 and LAT2. Recently it was shown that in tumour cells within the neutral amino acid transporter system L, the hLATl transporter (hLATl/h4F2hc heterodimeric membrane glycoproteins) is related to tumour growth and progression of malignant tumours. LAT1 expression was scarcely detected in non-tumour areas. LAT1 is highly expressed (up-regulated) in proliferating tissues, in particular malignant tumours, as it plays a critical role in cell growth and proliferation.
  • LAT2 transports all of the isomers of neutral alpha-amino acids by facilitated diffusion.
  • LAT2 has a high level of expression in small intestine, kidney, placenta, brain and in epithelia and blood-tissue barriers. LAT2 does not transport D-amino acids.
  • the tracers When evaluated in vivo in RIM tumour bearing rats, the tracers show high uptake in the tumour (comparable with the uptake of 3- 123 I-methyl ⁇ L-Tyr) while no renal accumulation or significant uptake in induced acute inflammatory tissue was observed.
  • the uptake and washout kinetics in vitro and in vivo were almost identical for both compounds.
  • 2- 123 I-L-Tyr is currently used in human studies. High uptake in tumours is observed while a fast clearance of the tracer by the kidneys to the bladder is observed. High selectivity is proven by the fact that the uptake in inflammatory lesions such as tuberculosis was negligible.
  • the inventors found that in the cancer cell lines rat RIM rhabdomyosarcoma, human HT29 and WiDr colon adenocarcinoma cells, A2058 melanin producing melanoma, C36 non-melanin producing melanoma and C6 glioma, used in the in vitro evaluation model, the uptake of both the enantiomeric L form and D form of neutral amino acids such as L-tyrosine (L-Tyr), D-tyrosine (D-Tyr), L-phenylalanine (L- Phe), D-Phe, 2-Br-L-Phe, 2-Br-D-Phe, 2-I-L-Phe, 2-I-D-Phe, 2-methyl-L-Phe, 2-methyl-D- Phe, L-Leucine,;H-L-Phe, I4 C-D-Phe,;H-L-Tyr, 2- 123 125 I-L-Tyr, 2- ,23
  • amino acid analogues such as 123 I-methyl-L-Tyr, 2- 123 I-L-Tyr, 2- 123 I-L-
  • This invention shows that the LAT1 transport system present in cancer cells, is a suitable transport system for the influx of neutral synthetic amino acids showing the D- enantiomeric form (D-amino acids) like the amino acids mentioned above.
  • the present invention is thus based on the finding that lipophilic neutral radioactively labelled synthetic amino acids showing the D enantiomeric form show a low, almost non-significant uptake in normal tissue and inflammatory tissue, show an uptake in tumour cells by the LAT amino acid transport system almost comparable with that of their L enantiomeric form analogues, which linked to a lower background uptake results in a better tumour to background ratio, and show a longer retention (slower efflux) in tumour cells than the L analogues due to their high specific activity and extreme low mass linked to a lower affinity than their L analogues vis-a-vis the LAT transport system (competition- retention model), making them appropriate candidates for systemic radionuclide tumour therapy.
  • the invention thus provides novel D-amino acid of the general formula NH 2 - CHR-COOH, wherein R is a variable side chain, for use in diagnosis with SPECT and PET or in systemic radionuclide radiotherapy, wherein the D-amino acid is labelled in the side chain R.
  • D-amino acids that are radioactively labelled in their R side chain have not been described before, in particular not for use in diagnosis and therapy.
  • R is a bidentate or tridentate bifunctional chelating molecule.
  • R is selected from the group consisting of benzyl, methyl benzyl, ethyl benzyl, 3-hydroxybenzyl or 4-hydroxybenzyl, either of which may be optionally substituted in a free ortho, meta, or para position with (CH 2 ) n -X, wherein n is 0, 1 or 2 and X is a radioactive halogen selected from F, CI, Br, I.
  • R is a polyamino polycarboxylic (PAPC) chelator that is optionally coupled to the D-amino acid via a spacer, and is in particular selected from the group consisting of histidine, DOTA, DTPA and EDTA.
  • PAPC polyamino polycarboxylic
  • R is a is a polyamino polycarboxylic (PAPC) chelator that is optionally coupled to the D- amino acid via a spacer, and is in particular selected from the group consisting of DOTA, DTPA and EDTA, and the radioactive label is complexed with the chelator.
  • the spacer is for example an alkyl group of the formula (CH 2 ) n - wherein n is 1-7, preferably 1-5.
  • radioactive isotopes 123 1, 99m Tc, m In, and 18 F are particularly useful as diagnostic radioisotopes.
  • 123 1, 99m Tc, m In emit gamma rays suitable for detection with SPECT
  • 18 F emits beta plus particles resulting in annihilation gamma rays of 51 IKeV detectable with PET.
  • the above mentioned D-amino acids are preferably labelled with ,31 I, 18 ⁇ /188 Re, 90 Y, 103 Pd, 177 Lu and m In because these isotopes emit radiation that causes cell death.
  • 2- ID-Phe are particularly suitable and for therapy 2- I-D-Tyr, 2- I-D-Phe are preferred.
  • Both tracers can be obtained by Cu assisted substitution in reducing conditions (Mertens et al. "Cu 1+ Assisted Nucleophilic Exchange Radiohalogenation: Application and Mechanistic Approach” in New Trends in Radiopharmaceutical Synthesis, Quality Assurance, and Regulatory Control, Editor: A.M .Emran, Plenum Press, NY, 1990, pp.
  • D-4-N,N-diethylamine-aminophenylalanine or D- ⁇ -4-EDTA-phenylalanine are custom synthesized D-analogues labelled with m In for both diagnosis and therapy or with 103 Pd, 90 Y, 177 Lu for therapy.
  • 2- 18 F-alkyl-D-phenylalanine can be obtained by nucleophilic aliphatic substitution of 18 F " on for example the tosylated precursor followed by mini-column purification.
  • the invention further relates to pharmaceutical compositions for use in diagnosis or therapy, comprising one or more radiolabelled D-amino acids of the invention and one or more suitable diluents, carriers, excipients or additives.
  • suitable diluents, carriers and excipients are for example 91 sodium chloride solution, 5% glucose solution, etc.
  • suitable supporting complexing agents and stabilizing agents well known in formulating radiopharmaceuticals are used.
  • the formulation of radiopharmaceuticals is well known to the person skilled in the art.
  • sterile kit formulations are used that are brought to the appropriate pH (4.5-7) and isotonicity as mentioned in Example 1 regarding labelling of 2-I-D-Phe.
  • sterile kit formulations are used that are brought to the appropriate pH (4.5-7) and isotonicity as mentioned in Example 1 regarding labelling of 2-I-D-Phe.
  • I purified (HPLC or multi mini-column system) 18 F-labelled compounds are used in isotonic saline.
  • a typical composition of the invention for use of 131 I-D-Phe in systemic radionuclide therapy is used in a kit formulation as mentioned in Example 1 diluted in isotonic saline and is used for both bolus injection and infusion.
  • the invention further relates to the use of the novel compounds in diagnosis with PET or SPECT or in systemic radionuclide therapy.
  • Figure 1 Uptake of 2- 125 I-D-Phe/2-I-D-Phe as function of time in different cancer cells.
  • Figure 3 "Slow” MEM stimulated efflux of 2- 125 I-D-Phe as compared to L- [ 3 H]-Phe.
  • Figure 4 Uptake of 2- 125 I-D-Phe/2-I-D-Phe in HEPES+ according to a Michaelis-Menten plot.
  • Figure 5 Lineweaver-Burk plot showing different lines for different concentrations of inhibiting compound with different slopes but the same intercept on the 1/mass-uptake axis.
  • Figure 7 Activity biodistribution in vivo as function of time. Planar camera acquisition.
  • Figure 8 Integral picture after 60 minutes of acquisition.
  • Figure 9 Planar acquisition RIM tumour bearing NuNu mouse.
  • 2-Iodo-D-phenylalanine (2-I-D-Phe) was prepared using the Cu 1+ non-isotopic exchange method (Mertens et al. Eur. J. Nucl Med (2002) 29(1):722; Lahoutte et al. JNucl Med. (2003) 44(9): 1489-94).
  • a 10 ml aqueous solution containing 30.3 mM 2-Br-L-phenylalanine (Peptech Corp., Burlington, Ma, USA), 4.46 mM CuS0 4 (Merck), 8.9 mM citric acid (Merck), 9.0 mM SnS0 4 (Merck), 10.7 mM gentisic acid (Merck) and 44.5 mM Nal (Merck) was added.
  • the solution is flushed with N 2 for 10 minutes and heated at 160EC for 16h under N 2 atmosphere. After centrifugation the solution containing the product was transferred to a new flask and the water was evaporated.
  • reaction vial placed in a septum-closed safety container was heated at 100EC during 60 minutes.
  • the reaction mixture followed by 500 ⁇ l of a 71 mM Na 3 -citrate solution was passed through a sterile 0.22 ⁇ m Ag-membrane filter (Millipore).
  • the non radioactive amino acids used were: L-Tyr, D-Tyr, L-Phe, 2-Br-L-Phe, 2-Br-D-Phe, 2-I-L-Phe, 2-I-D-Phe, 2-L-methyl-Phe, 2-D-methyl-Phe.
  • radioactively labelled amino acid analogues were: ; H-L-Phe, 14 C-D- Phe, ; H-L-Tyr, 2- ' I-L-Tyr, 2- " I-L-Phe as references and the new compound 2- 123/125 I-D-Phe.
  • FBS Foetal Bovine Serum
  • FBS Foetal Bovine Serum
  • penicillin Invitrogen
  • streptomycin Invitrogen
  • cells were cultivated in 6-well-plates (NUNC) for 2 days until adhesive mono-layers, containing about 4 ( ⁇ 0.2) million cells per well were obtained.
  • the process was terminated by physical withdrawal of the buffer and washing three times with ice-cold phosphate-buffered saline (PBS). Subsequently, the cells were detached from the well with 2 mL of 0.1 M NaOH. The radioactivity of the samples was counted using a gamma-counting-system (Cobra-inspector 5003, Canberra Packard, Meriden, CT, USA).
  • the cells were incubated for times ranging from 1 to 20 minutes in 1 ml of 0.1 mM 2-I-L-Phe in HEPES + and HEPES " or MEM containing 37 KBq 2-[ 125 I]-D-Phe.[' 4 C]- D-phenylalanine (Amersham Biosciences) was used as reference product. Saturation of the uptake was measured at 15 min with concentrations of 2-I-D-Phe varying from 0.01 to 0.2 mM.
  • Ki apP a ⁇ e n t is the combination of the Km values related to the transport system(s) involved.
  • the cells were incubated with 37 KBq 2- 125 I-L-Phe for 15 minutes in HEPES+ and HEPES- buffer. The incubation medium was removed and the cells were washed tliree times with ice-cold PBS. Subsequently HEPES buffer containing 5 mM L-Phe or 5mM BCH or MEM buffer was added. The efflux medium was removed after 20 minutes, the cells were washed tliree times with ice-cold PBS, detached with 0.1 M NaOH, suspended and counted.
  • Wag/Rij rats and NuNu mice were subcutaneously injected in the right flank with 1 million RIM rhabdomyosarcoma cells (Harlan, Netherlands). Tumours were grown for 4 weeks.
  • the animals had free access to water and food until 4 hours before tracer injection.
  • the animals were anaesthetised (halothane orNembutal). Afterwards the animals were sacrificed by intravenous injection of KC1.
  • the study protocol was approved by the ethical committee for animal studies and the National Institutes of Health principles of laboratory animal care (NIH publication 86-23, revised 1985) were followed.
  • the animals were injected with 5MBq 2- 125 I-D-Phe and sacrificed 10 minutes post injection.
  • the organs and tissues of interest were removed rapidly, washed and weighed.
  • the radioactivity of the samples was counted by use of a gamma ray counting system.
  • the amount of radioactivity in the samples is expressed as differential absorption ratio (activity per gram of sample divided by the activity injected per gram rat)
  • Dynamic imaging of the rat injected in the penis vein was performed with a gamma camera equipped with a medium energy collimator (resolution 11 mm at full width at half maximum). Imaging was started immediately after I.V. injection of 18.5 Mbq 2- 123 I- D-Phe. A total of 240 images of 10 s each were acquired in 128X128 matrices with a zoom factor 302 (pixel size 1.5 mm) and a photo peak window set around 159 KeV.
  • DUR differential uptake ratio
  • the uptake in MEM mimics in vivo conditions in blood as MEM contains about 1.2 mM amino acids, which are known to be transported by the L transport system.
  • tumour it is somewhat lower for the D form but still a good tumour/blood ratio is obtained.
  • Fig. 7 shows the bio-distribution as a function of time measured with planar camera acquisition.
  • the accumulated picture after 60 minutes shows a clear uptake in the tumour and a fast clearance through the lddneys to the bladder.
  • Fig. 9 shows that the uptake (counts per pixel) in a RIM tumour bearing NuNu mice of 2- 123 I-D-Phe measured by means of SPECT acquisition of ⁇ 5%ID/pixel.
  • a high uptake in the tumour is observed while the clearance of the tracer occurs mostly through the lddneys to the bladder.
  • No significant uptake in the thyroid shows that the deiodination is negligible. This distribution is comparable with the uptake of 2- 123 I-L-Phe in the same mice.
  • Fig. 10 shows that in vivo in NuNu mice the uptake in human A2058 melanoma cells the tumour/backgiOund ratio amounts up to 5 allowing SPECT acquisition of these rumours.
  • This SPECT acquisition represented in Fig. 10, shows a high uptake in the tumour and a large clearance through the lddneys to the bladder. Here also no significant uptake in the thyroid is observed. Stability and lack of deiodination is of prime importance for radioiodinated ( 131 I) compounds used for therapeutic purposes.
  • the amino acid derivatization procedure can also be applied to conjugate different kinds of chelator e.g. DTP A, DOTA, etc, useful for coordination to other radioisotopes like In-I l l, Y-90, Lu-177.

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Abstract

L'invention concerne l'acide aminé de type D de la formule générale NH2-CHR-COOH, dans laquelle R représente une chaîne latérale variable. Cet acide aminé de type D est utilisé pour la tomographie monophotonique d'emission et la tomographie par émission de positons ainsi que dans la radiothérapie isotopique systémique. L'acide aminé de type D est marqué dans la chaîne latérale R qui est, de préférence, du benzyle, méthyle benzyle, éthyle benzyle, 3-hydroxybenzyle ou 4-hydroxybenzyle, l'un des deux pouvant facultativement être substitué par (CH2)n-X dans une position ortho, méta ou para libre, n représentant 0, 1 ou 2 et X représentant un halogène radioactif sélectionné parmi F, Cl, Br, I ou un chélateur polycarboxylique polyamino (PAPC). L'invention concerne également des compositions pharmaceutiques utilisées dans le diagnostic et la thérapie du cancer.
PCT/US2004/003829 2003-02-11 2004-02-11 Acides amines de type d radiomarques, utilises pour la tomographie monophotonique d'emission et la tomographie par emission de positons ainsi que dans la therapie isotopique systemique WO2004071505A2 (fr)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070128108A1 (en) * 2005-11-18 2007-06-07 Samuel Samnick Therapy of malignant neoplasias
US20100278732A1 (en) * 2009-05-01 2010-11-04 Washington University 1h-[1, 2, 3] triazole substituted amino acids and uses thereof
US20120093726A1 (en) * 2009-03-24 2012-04-19 Andrew Katsifis Radiolabeled Fluorine Derivatives of Methionine

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR1581849A (fr) * 1967-09-11 1969-09-19
GB2020275A (en) * 1978-04-27 1979-11-14 Henning Berlin Gmbh Radioactive Carboxylic Acid Derivatives and Processes for Their Manufacture
WO2001082975A2 (fr) * 2000-04-25 2001-11-08 Washington University Complexes peptidiques permeables aux membranes pour l'imagerie medicale, les diagnostics, et la therapie pharmaceutique
WO2003099746A1 (fr) * 2002-05-25 2003-12-04 Abx Gmbh Procede pour produire des acides amines alpha fluores au 18f

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR1581849A (fr) * 1967-09-11 1969-09-19
GB2020275A (en) * 1978-04-27 1979-11-14 Henning Berlin Gmbh Radioactive Carboxylic Acid Derivatives and Processes for Their Manufacture
WO2001082975A2 (fr) * 2000-04-25 2001-11-08 Washington University Complexes peptidiques permeables aux membranes pour l'imagerie medicale, les diagnostics, et la therapie pharmaceutique
WO2003099746A1 (fr) * 2002-05-25 2003-12-04 Abx Gmbh Procede pour produire des acides amines alpha fluores au 18f

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
FOULON C F ET AL: "RADIOIODINATION VIA D-AMINO ACID PEPTIDE ENHANCES CELLULAR RETENTION AND TUMOR XENOGRAFT TARGETING OF AN INTERNALIZING ANTI-EPIDERMAL GROWTH FACTOR RECEPTOR VARIANT III MONOCLONAL ANTIBODY" CANCER RESEARCH, AMERICAN ASSOCIATION FOR CANCER RESEARCH, BALTIMORE, MD, US, vol. 60, 15 August 2000 (2000-08-15), pages 4453-4460, XP000938356 ISSN: 0008-5472 *
HEISS, PETER ET AL: "Investigation of transport mechanism and uptake kinetics of O-(2-[18FÜfluoroethyl)-L-tyrosine in vitro and in vivo" JOURNAL OF NUCLEAR MEDICINE , 40(8), 1367-1373 CODEN: JNMEAQ; ISSN: 0161-5505, 1999, XP002290177 *
ISHIWATA K ET AL: "SYNTHESIS AND RADIATION DOSIMETRY OF 4-BORONO-2-(18F)FLUORO-D,L- PHENYLALANINE: A TARGET COMPOUND FOR PET AND BORON NEUTRON CAPTURE THERAPY" APPLIED RADIATION AND ISOTOPES, INTERNATIONAL JOURNAL OF RADIATION APPLICATIONS AND INSTRUMENTATION, PART A, PERGAMON PRESS LTD, GB, vol. 42, no. 2, 25 June 1990 (1990-06-25), pages 325-328, XP000916788 ISSN: 0883-2889 *
KAWAI, KEIICHI ET AL: "Monoiodo- D - tyrosine , an artificial amino acid radiopharmaceutical for selective measurement of membrane amino acid transport in the pancreas" NUCLEAR MEDICINE AND BIOLOGY , 17(4), 369-76 CODEN: NMBIEO; ISSN: 0883-2897, 1990, XP009034344 *
WESTER, HANS J. ET AL: "Synthesis and radiopharmacology of O-(2-[18FÜfluoroethyl)-L-tyrosine for tumor imaging" JOURNAL OF NUCLEAR MEDICINE , 40(1), 205-212 CODEN: JNMEAQ; ISSN: 0161-5505, 1999, XP002290178 *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070128108A1 (en) * 2005-11-18 2007-06-07 Samuel Samnick Therapy of malignant neoplasias
US9682158B2 (en) * 2005-11-18 2017-06-20 Samuel Samnick Therapy of malignant neoplasias
US20120093726A1 (en) * 2009-03-24 2012-04-19 Andrew Katsifis Radiolabeled Fluorine Derivatives of Methionine
US20100278732A1 (en) * 2009-05-01 2010-11-04 Washington University 1h-[1, 2, 3] triazole substituted amino acids and uses thereof
US8722014B2 (en) * 2009-05-01 2014-05-13 Washington University 1 H-[1, 2, 3] triazole substituted amino acids and uses thereof

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